KAT6A
Domain
The N-terminus is involved in transcriptional activation while the C-terminus is involved in transcriptional repression.
Function
Histone acetyltransferase that acetylates lysine residues in histone H3 and histone H4 (in vitro). Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity. May act as a transcriptional coactivator for RUNX1 and RUNX2. Acetylates p53/TP53 at 'Lys-120' and 'Lys-382' and controls its transcriptional activity via association with PML.
Involvement in disease
Chromosomal aberrations involving KAT6A may be a cause of acute myeloid leukemias. Translocation t(8;16)(p11;p13) with CREBBP (PubMed:8782817). Translocation t(8;22)(p11;q13) with EP300 (PubMed:10824998). KAT6A-CREBBP may induce leukemia by inhibiting RUNX1-mediated transcription (PubMed:11742995). Inversion inv(8)(p11;q13) generates the KAT6A-NCOA2 oncogene, which consists of the N-terminal part of KAT6A and the C-terminal part of NCOA2/TIF2. KAT6A-NCOA2 binds to CREBBP and disrupts its function in transcription activation (PubMed:12676584).
A chromosomal aberration involving KAT6A is a cause of therapy-related myelodysplastic syndrome. Translocation t(2;8)(p23;p11.2) with ASXL2 generates a KAT6A-ASXL2 fusion protein.
Arboleda-Tham syndrome
ARTHS
An autosomal dominant disorder characterized by intellectual disability, dysmorphic facial features, delayed psychomotor development, and lack of speech.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Autoacetylation at Lys-604 is required for proper function (By similarity). Autoacetylated.
Phosphorylation at Thr-369 by PKB/AKT1 inhibits its interaction with PML and negatively regulates its acetylation activity towards p53/TP53.
Sequence Similarities
Belongs to the MYST (SAS/MOZ) family.
Cellular localization
- Nucleus
- Nucleus
- Nucleolus
- Nucleus
- Nucleoplasm
- Nucleus
- PML body
- Recruited into PML body after DNA damage.
Alternative names
MOZ, MYST3, RUNXBP2, ZNF220, KAT6A, Histone acetyltransferase KAT6A, Monocytic leukemia zinc finger protein, Runt-related transcription factor-binding protein 2, Zinc finger protein 220, MYST-3